Single nucleotide polymorphisms (SNPs) in 7000 bp of the mitochondrial genome, encompassing 15 coding regions from COI to ND5, were characterized by single strand polymorphism analysis and confirmed by DNA sequencing. About 2.4% of normozoospermic men and 8.4% of men with poor semen quality had at least one nucleotide substitution. Most of the substitutions occurred in the third codon and did not change the amino acid. Hydrophobicity plots of the proteins with changes in an amino acid as a result of a nucleotide substitution suggested that they did not affect the function of the protein. The two most common substitutions at nucleotide (nt) 9055 and 11719 had significantly higher frequencies in men with reduced sperm motility. Eleven percent of the men with poor semen parameters and 1.3% of normozoospermic men had a 9055 substitution, 12% of the men with poor semen parameters had a substitution at nt 11719, but none of the normozoospermic men had this substitution. All the patients with these substitutions had reduced sperm motility and/or low sperm count. These SNPs in the mitochondrial genome were in a homoplasmic state. Thus, we propose that possessing these mitochondrial mutations compromises the semen quality of these men.

Thyroid hormones are essential for vertebrate development. There is a characteristic rise in thyroid hormone levels in blood during critical periods of thyroid hormone-regulated development. Thyroid hormones are lipophilic compounds, which readily partition from an aqueous environment into a lipid environment. Thyroid hormone distributor proteins are required to ensure adequate distribution of thyroid hormones, throughout the aqueous environment of the blood, and to counteract the avid partitioning of thyroid hormones into the lipid environment of cell membranes. In human blood, these proteins are albumin, transthyretin and thyroxine-binding globulin. We analyzed the developmental profile of thyroid hormone distributor proteins in serum from a representative of each order of marsupials ( M. eugenii; S.crassicaudata), a reptile ( C. porosus), in two species of salmonoid fishes ( S. salar; O. tshawytsch), and throughout a calendar year for sea bream ( S. aurata). We demonstrated that during development, these animals have a thyroid hormone distributor protein present in their blood which is not present in the adult blood. At least in mammals, this additional protein has higher affinity for thyroid hormones than the thyroid hormone distributor proteins in the blood of the adult. In fish, reptile and polyprotodont marsupial, this protein was transthyretin. In a diprotodont marsupial, it was thyroxine-binding globulin. We propose an hypothesis that an augmented thyroid hormone distributor protein network contributes to the rise in total thyroid hormone levels in the blood during development.

This study reports the first clearly defined heteroplasmic mutation in immature human sperm cells. The human sperm mitochondrial genome from residue 8186-9341 was analysed with the aim of identifying point mutations which may be associated with human male infertility. The semen samples analysed were obtained from 88 fertile men, 19 with oligozoospermia, and 12 with severe oligozoospermia. Using single strand conformation polymorphism analysis a heteroplasmic T to C transition was detected in the ATPase6 gene, at nucleotide position 8821, in semen samples from one out of 12 (8%) severely oligozoospermic men, but not in oligozoospermic men or normospermic men. This mutation changed the amino acid serine to proline at residue 99 of the mitochondrial ATPase6 in a region which is highly conserved in other vertebrates including rat, bovine, chicken, salmonids and Xenopus. The mutation was detected in semen samples collected from the same man 9 months apart and in peripheral blood lymphocytes. Single sperm cell analyses did not find this mutation in the mature sperm, but the mutation was detected in 7% of immature spermatids. Our finding suggests that immature spermatids with this mutation fail to develop fully.

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